Source Citation

Abstract

Question

Do cohort studies show that iron levels at baseline are associated with an increased
risk for coronary heart disease?

Data sources

Studies were identified by using MEDLINE with search terms related to iron status
(iron, ferritin, and transferrin) and coronary heart disease (CHD, myocardial infarction,
atherosclerosis, and vascular disease). Bibliographies of relevant studies were scanned,
important journals were hand searched, and authors were contacted.

Study selection

Cohort studies were selected if they had long-term follow-up and reported correlations
between iron status at baseline and the development of coronary heart disease.

Main results

12 studies that included 7800 cases of coronary heart disease met the inclusion criteria.
Several studies provided data using ≥ 1 test for iron status: 5 studies used serum
ferritin, 5 studies used transferrin saturation, 4 studies used total iron-binding
capacity, 3 studies used serum iron levels, and 3 studies used dietary questionnaires.
Analysis for all studies compared participants in the top third of iron levels at
baseline with participants in the bottom third except for studies of serum ferritin,
which compared levels of ≥ 200 with < 200 µg/L. All studies but 1 adjusted for
smoking and other cardiovascular risk factors. No important association was shown
between iron levels measured by any method and coronary heart disease (Table).

Conclusion

Baseline iron levels are not associated with an increased risk for the development
of coronary heart disease.

Commentary

Many epidemiologic studies have examined the relation between coronary heart disease
and such biochemical markers as fibrinogen and C-reactive protein levels, antibodies
to various infective agents, and iron status. This meta-analysis of prospective studies
by Danesh and Appleby concluded that no evidence supports a relation between coronary
heart disease and baseline iron levels.

The initial theory that iron levels were associated with coronary heart disease was
based on its role in lipid peroxidation. Super-oxide radicals generate iron from ferritin
(1), and metal ions seem to be required for the peroxidation of low-density lipoprotein
cholesterol by macrophages (2). The studies reviewed in this meta-analysis addressed many types of iron stores,
including ferritin levels (which are assumed to be the most accurate); transferrin
saturation; iron-binding capacity; and iron intake (through questionnaires). None
of the combined analyses found a strong relation between any measure of iron status
and the presence of coronary heart disease. This may be because of the effect that
inflammation had on iron-carrying proteins and the marked individual variation in
levels over time. The possible confounding effect by markers of inflammation is suggested
by the known relation to fibrinogen levels, C-reactive protein levels, and leukocyte
count reviewed in another meta-analysis done in 1998 by Danesh (an author of this
study) and colleagues (3).

Some of the included studies did raise the question of a relation between acute myocardial
infarction and iron levels while agreeing that coronary heart disease was not associated
with iron levels. The relation between iron and myocardial infarction was not present
in men using vitamin E but was higher in those with other traditional risk factors
(4). The role of iron in our understanding of coronary heart disease as it relates to
oxidative stress, perhaps, has still not been answered.